Donor specific unresponsiveness to organ allografts remains an illusive goal in clinical cadaveric transplantation, as most successful experimental protocols for the production of antigen-specific immunosuppression require lengthy recipient pretreatment. The use of an induction course of anti-lymphocyte serum (ALS) beginning at the time of transplantation, followed by the transfusion to the recipient of donor specific bone marrow, has been shown to induce prolonged allograft survival in animals and is applicable in clinical cadaveric transplantation. Our preliminary data in humans suggests that the transfusion of cryopreserved cadaver bone marrow following a short course of ALS is safe and does not induce graft versus host disease or allograft rejection. Thus far, 57 patients have received cadaveric renal allografts and ALG followed by the transfusion of cryopreserved donor specific bone marrow. 54 patients have received the contralateral kidney and similar immunosuppression without the marrow transfusion and serve as controls. The median followup in both groups is 16 months, (range 2.5 to 33 months). The graft survival rate for the bone marrow group at 12 and 18 months is 90% (confidence limits (CL) 85-94) and 85% (CL78-90) respectively. In the control group the 12 and 18 month allograft survival rate was 71% (CL 63-78) and 67% (CL 58-74) respectively (p=0.007). Mixed lymphocyte culture analysis shows a trend to diminish donor specific responsiveness in the bone marrow group. Analysis of peripheral blood lymphocytes of marrow transfused patients indicate the persistence of chimerism in some patients at least one year following transfusion as demonstrated by polymerase chain reaction. We propose to expand this single center experience to a multicenter trial in which donor specific bone marrow will be transfused in a prospective randomized fashion to renal allograft recipients following an induction course of use of donor marrow transfusion may be adaptable to a variety of induction protocols.